7MPA
Structure and topology of DWORF in bicelles by oriented solid-state NMR
Summary for 7MPA
| Entry DOI | 10.2210/pdb7mpa/pdb |
| NMR Information | BMRB: 50778 |
| Descriptor | Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF (1 entity in total) |
| Functional Keywords | regulin, miniprotein, sarcoplasmic reticulum, oriented solid state nmr spectroscopy, chemical shift anisotropy, dipolar coupling, separated local field, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 3908.82 |
| Authors | Reddy, U.V.,Weber, D.K.,Veglia, G.V. (deposition date: 2021-05-04, release date: 2021-06-30, Last modification date: 2024-05-15) |
| Primary citation | Reddy, U.V.,Weber, D.K.,Wang, S.,Larsen, E.K.,Gopinath, T.,De Simone, A.,Robia, S.,Veglia, G. A kink in DWORF helical structure controls the activation of the sarcoplasmic reticulum Ca 2+ -ATPase. Structure, 30:360-, 2022 Cited by PubMed Abstract: SERCA is a P-type ATPase embedded in the sarcoplasmic reticulum and plays a central role in muscle relaxation. SERCA's function is regulated by single-pass membrane proteins called regulins. Unlike other regulins, dwarf open reading frame (DWORF) expressed in cardiac muscle has a unique activating effect. Here, we determine the structure and topology of DWORF in lipid bilayers using a combination of oriented sample solid-state NMR spectroscopy and replica-averaged orientationally restrained molecular dynamics. We found that DWORF's structural topology consists of a dynamic N-terminal domain, an amphipathic juxtamembrane helix that crosses the lipid groups at an angle of 64°, and a transmembrane C-terminal helix with an angle of 32°. A kink induced by Pro15, unique to DWORF, separates the two helical domains. A single Pro15Ala mutant significantly decreases the kink and eliminates DWORF's activating effect on SERCA. Overall, our findings directly link DWORF's structural topology to its activating effect on SERCA. PubMed: 34875216DOI: 10.1016/j.str.2021.11.003 PDB entries with the same primary citation |
| Experimental method | SOLID-STATE NMR |
Structure validation
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